There is an enormous interest in the application of diverse chemical and biological tools to control the expression of specific genes or compromise the activities of specific mRNAs and proteins. The biotechnology industry develops these tools for plant and animal engineering, the pharmaceutical industry makes use of these tools to validate drug targets, and the medical community investigates a subset of these reagents as therapeutics in their own right. The purpose of this Keystone Symposium is to review the utility of chemical and biological approaches to selectively turning gene activity off at the transcriptional, post-transcriptional and protein level- especially with reference to functional genomics. The aim is to provide a broad overview of established and emerging methodologies, the basic science behind these approaches and their utility from an industrial and medical perspective. The availability of the human genome and widespread use of micro array strategies for assessing specificity should make the meeting especially timely and provide a unifying focus by 2003. The latest advances on RNA interference, protein engineering to repress transcription, chemical approaches to gene control, antisense, ribozymes and knockout strategies will be discussed.